Infant formula with cow\u2019s milk fat and prebiotics affects intestinal flora, but not the incidence of infections during infancy in a double-blind randomized controlled trial

Antonia Nomayo,Josef Tvrdik,Rainer Rossi,Richard Zelenka,Janine Foster,Katharina Timme,Andreas Schwiertz,Frank Jochum

doi:10.1186/s40348-020-00098-1

Abstract

BackgroundThe postnatal intestinal colonization of human milk-fed and formula-fed infants differs substantially, as does the susceptibility to infectious diseases during infancy. Specific ingredients in human milk, such as prebiotic human milk oligosaccharides and a specifically structured fat composition with high proportion of beta-palmitic acid (beta-PA) promote the growth of intestinal bifidobacteria, which are associated with favorable effects on infants’ health. The present study investigates whether addition of prebiotic galactooligosaccharides (GOS) in combination with higher amounts of beta-PA from cow’s milk fat in infant formula positively affects gut microbiota and the incidence of infections in formula-fed infants.MethodsIn a double-blind controlled trial, formula-fed infants were randomly assigned to either receive an experimental formula containing a higher proportion of beta-PA (20–25%) from natural cow’s milk fat, and a prebiotic supplement (0.5 g GOS/100 ml), or a standard infant formula with low beta-PA (< 10%), without prebiotics. A breast-fed reference group was also enrolled. After 12 weeks, fecal samples were collected to determine the proportion of fecal bifidobacteria. The number of infections during the first year of life was recorded.ResultsAfter 12 weeks, the proportion of fecal bifidobacteria was significantly higher in infants receiving formula with high beta-PA and GOS compared to control, and was similar to the breast-fed group (medians 8.8%, 2.5%, and 5.0% respectively; p < 0.001). The incidence of gastrointestinal or other infections during the first year of life did not differ between groups.ConclusionsThe combination of higher amounts of beta-PA plus GOS increased significantly the proportion of fecal bifidobacteria in formula-fed infants, but did not affect the incidence of infections.Trial registrationThe study protocol was registered with Clinical Trials (Protocol Registration and Results System Trial ID: NCT01603719) on 05/15/2012 (retrospectively registered).

Highlights

The postnatal intestinal colonization of human milk-fed and formula-fed infants differs substantially, as does the susceptibility to infectious diseases during infancy
Possible confounders on the primary outcomes, like gestational age, perinatal antibiotic treatment, and birth mode were evenly distributed with no significant differences between groups, except that parents in the breast milk group significantly more often had higher school education, and BF group tended to have higher proportion of children delivered by cesarean section (CS) than both formula groups
Attrition was considerably higher than estimated; 39% of the study participants in the formula groups and 47% in the BF group discontinued the study before 12 weeks

Summary

Introduction

The postnatal intestinal colonization of human milk-fed and formula-fed infants differs substantially, as does the susceptibility to infectious diseases during infancy. In addition to various other ingredients, human milk oligosaccharides (HMOs), originally identified as the “bifidus factor” in human breast milk, are believed to contribute to this benefit by supporting the growth of health-promoting bifidobacteria [1, 2, 5]. This presumably has positive effects on intestinal maturation and immunity development [6, 7]. These differences in bacterial colonization have been demonstrated using both molecular and culture-based detection techniques [1, 8,9,10]

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Results

Discussion

Conclusion